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Publication : Triggering of TNFRSF25 promotes CD8⁺ T-cell responses and anti-tumor immunity.

First Author  Slebioda TJ Year  2011
Journal  Eur J Immunol Volume  41
Issue  9 Pages  2606-11
PubMed ID  21688261 Mgi Jnum  J:176986
Mgi Id  MGI:5293270 Doi  10.1002/eji.201141477
Citation  Slebioda TJ, et al. (2011) Triggering of TNFRSF25 promotes CD8(+) T-cell responses and anti-tumor immunity. Eur J Immunol 41(9):2606-11
abstractText  TNFRSF25 is a member of the TNF receptor superfamily (TNFRSF) that binds to the TNF-like protein TL1A. Although recent studies have demonstrated a role for TNFRSF25 in regulating CD4(+) T-cell responses, it remains to be determined if TNFRSF25 functions as a costimulatory receptor for CD8(+) T cells. Here, we demonstrate that ectopic expression of TL1A on mouse plasmacytomas promotes elimination of tumor cells in a CD8(+) T-cell-dependent manner and renders mice immune to a subsequent challenge with tumor cells. To gain further insight into the role of TNFRSF25 in CD8(+) T-cell responses, we analyzed the effect of TNFRSF25 triggering on OT-I TCR transgenic T cells. We demonstrate that TNFRSF25 triggering in vivo with soluble TL1A promotes the proliferation and accumulation of antigen-specific CD8(+) T cells as well as their differentiation into CTLs. Furthermore, we show that TNFRSF25 also functions as a costimulatory receptor for memory CD8(+) T cells. Thus, TNFRSF25 triggering enhances the secondary expansion of endogenous antigen-specific memory CD8(+) T cells. Our data suggest that TNFRSF25 agonists, such as soluble TL1A, could potentially be used to enhance the immunogenicity of vaccines that aim to elicit human anti-tumor CD8(+) T cells.
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